1. Field of the Invention
The present invention relates generally to the fields of bone and cartilage physiology as well as the treatment of tumors and cysts. More specifically, the invention refers to the use of a formulation for the growth of bone and cartilage and the treatment of periodontium, tumors and cysts of the jaw and uses thereof.
2. Description of the Related Art
Osteoarthritis is a degenerative joint disease involving the symptomatic loss of cartilage in load-bearing areas of the joint and is frequently found in the temporomandibular joint, knee, hip, hand, foot and spine. Osteoarthritis causes significant pain and leads to disability and a decrease in the quality of life. Treatment includes orthotics and foot wear, physical therapy and exercise, gnathological dental prosthesis and occlusal plates (jaw), pharmacologic therapies such as hyaluronan derivatives and corticosteroids. Surgical management includes osteotomies, partial or total replacement of damaged articulation and autologous chondrocyte implantation, which can only provide a short-lived reduction in symptoms. Cartilage re-growth may be the ideal solution, but until now, is only used for small defects in specific areas of the femoral cartilage due to the expense and length of time required for cartilage re-growth. The cost of surgical treatments is very high and most of the time, the results do not meet expectations.
The basic management of long bone fractures involves its immobilization to ensure consolidation. Fracture repair could fail due to several reasons. For example, pseudarthrosis occurs when bone consolidation is not achieved after a bone fracture. It is caused by osteotomy or fracture instability, infection and/or loss of bone mass after comminuted fractures. Common treatments include physical therapy, pulsed electromagnetic field, medication with bisphosphonates, curettage of involved bone segments with or without bone graft and circular external fixation. Osteoporosis is a skeletal disorder characterized by compromised bone strength that increases the risk of fracture and also causes a delay in the consolidation of fractures. Current treatment includes the administration of bi- or polyphosphonates, that reduce bone resorption and bone turnover with side effects such as esophageal or gastric irritation, osteonecrosis of the jaw and atypical femoral fractures. Thus, new effective and non-harmful alternative treatments are needed.
The goals in treating midface fractures are to restore harmonious occlusion between the maxilla and mandible to obtain postoperative chewing function and reestablish mid-facial height and facial symmetry. In midface and mandibular fractures, dental occlusion is the most important parameter in reestablishing facial contour and reduction of the fracture. Fracture of the alveolar process is a common injury and nearby soft tissues and teeth are often damaged. The aim of dentoalveolar fracture treatment is to re-establish the normal form and function of the masticatory system. Until now, the only treatment for compromised pulp and/or nerve of the teeth is a root canal, and in recurrent or more severe cases, dental extraction.
Tumors and cysts of the jaw are very common, have a high rate of recurrence, and are classified as odontogenic and non-odontogenic. Among the odontogenic cysts, follicular (dentigerous) cysts are particularly aggressive as they cause root resorption of adjacent teeth in more than 50% of cases. A follicular cyst is composed of a membranous sac or capsule that destroys adjacent bone tissue. Odontoma, a common odontogenic tumor, frequently interferes with teeth eruption.
Ameloblastoma is a benign but locally aggressive odontogenic tumor with high recurrence rates which can occur from the epithelial lining of a follicular cyst. The mandible is commonly affected including the ascending ramus, the premolar region and the anterior region, and some ameloblastomas are associated with an unerupted tooth. Ameloblastoma is observed as a radiolucent area presented in a multilocular or unilocular pattern and can be either completely radiolucent or radiolucent with septa. It causes extensive root resorption and displacement of teeth and has considerable potential for bone expansion. Surgical treatment may involve resection of the jaw or radiation therapy for inoperable tumors.
Non-odontogenic cysts include aneurysmal bone cysts and globulomaxillary cysts. The aneurysmal bone cyst is a rare benign lesion of the craniofacial bone which rapidly grows into a bony expansion. The globulomaxillary cyst is a fissural cyst which causes divergence of teeth roots. Treatment consists of surgical curettage or complete excision of the lesion.
The microenvironment of cysts and tumors has recently become a target for new treatments. The tumor's microenvironment is an integral part of its anatomy, physiology and functionality and is made of stem cells, soluble factors, signaling molecules, and extracellular matrix. Furthermore, the feasibility of differentiating stem cells into specialized cells or tissues by mechanical stimuli and/or chemical and biological substances has become evident, especially for tissue engineering applications.
Tissue engineering has the aim of inducing specific cell proliferation or to reprogram cells to heal or achieve tissue regeneration for clinical applications. Tissue engineering techniques include inductive tissue engineering (local delivery of growth factors to stimulate local cells and induce regeneration), conductive tissue engineering (use of a matrix or biomaterials to stimulate growth of existing tissue, cell transplantation (direct introduction of tissue previously manipulated in vitro, and hybrid tissue engineering (implantation of an in vitro “prepared” biomaterial within stem cells and growth factors).
Currently, there is no tissue engineering technique, formulation, or minimally invasive methodology or clinical procedure that works with the intralesional microenvironment to ensure even partial regeneration of injured bone, cartilage, teeth or periodontium or treatment of tumoral or cystic lesions of the jaw to promote regeneration of damaged tissues. Thus, the prior art is deficient in formulations and methods achieving these effects. The present invention fulfills this longstanding need and desire in the art.